Quantum Chemical Study of a Radical Relay Mechanism for the HydG-Catalyzed Synthesis of a Fe(II)(CO)2(CN)cysteine Precursor to the H-Cluster of [FeFe] Hydrogenase,Biochemistry

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Quantum Chemical Study of a Radical Relay Mechanism for the HydG-Catalyzed Synthesis of a Fe(II)(CO)2(CN)cysteine Precursor to the H-Cluster of [FeFe] Hydrogenase
Biochemistry ( IF 2.9 ) Pub Date : 2021-09-27 , DOI: 10.1021/acs.biochem.1c00379
Nanhao Chen ₁ , Guodong Rao ₁ , R David Britt ₁ , Lee-Ping Wang ₁

Affiliation

The [FeFe] hydrogenase catalyzes the redox interconversion of protons and H₂ with a Fe–S “H-cluster” employing CO, CN, and azadithiolate ligands to two Fe centers. The biosynthesis of the H-cluster is a highly interesting reaction carried out by a set of Fe–S maturase enzymes called HydE, HydF, and HydG. HydG, a member of the radical S-adenosylmethionine (rSAM) family, converts tyrosine, cysteine, and Fe(II) into an organometallic Fe(II)(CO)₂(CN)cysteine “synthon”, which serves as the substrate for HydE. Although key aspects of the HydG mechanism have been experimentally determined via isotope-sensitive spectroscopic methods, other important mechanistic questions have eluded experimental determination. Here, we use computational quantum chemistry to refine the mechanism of the HydG catalytic reaction. We utilize quantum mechanics/molecular mechanics simulations to investigate the reactions at the canonical Fe–S cluster, where a radical cleavage of the tyrosine substrate takes place and proceeds through a relay of radical intermediates to form HCN and a COO^•– radical anion. We then carry out a broken-symmetry density functional theory study of the reactions at the unusual five-iron auxiliary Fe–S cluster, where two equivalents of CN^– and COOH^• coordinate to the fifth “dangler iron” in a series of substitution and redox reactions that yield the synthon as the final product for further processing by HydE.

中文翻译：

氢气催化合成 Fe(II)(CO)2(CN) 半胱氨酸前体到 [FeFe] 氢化酶 H 簇的自由基中继机制的量子化学研究

[FeFe] 氢化酶催化质子和 H ₂与 Fe-S“H-簇”的氧化还原相互转化，使用 CO、CN 和氮杂二硫醇配体到两个 Fe 中心。H 簇的生物合成是一个非常有趣的反应，由一组称为 HydE、HydF 和 HydG 的 Fe-S 成熟酶进行。HydG 是自由基S -腺苷甲硫氨酸 (rSAM) 家族的成员，可将酪氨酸、半胱氨酸和 Fe(II) 转化为有机金属 Fe(II)(CO) ₂(CN) 半胱氨酸“合成子”，用作 HydE 的底物。尽管 HydG 机制的关键方面已通过同位素敏感光谱方法通过实验确定，但其他重要的机械问题仍未通过实验确定。在这里，我们使用计算量子化学来改进 HydG 催化反应的机制。我们利用量子力学/分子力学模拟来研究典型 Fe-S 簇的反应，其中酪氨酸底物发生自由基裂解，并通过自由基中间体的接力进行，形成 HCN 和 COO ^•-自由基阴离子。然后，我们对不寻常的五铁辅助 Fe-S 团簇的反应进行了对称性破缺密度泛函理论研究，其中两个当量的 CN ^-和 COOH ^•在一系列取代和氧化还原反应中与第五个“吊环铁”配位，产生合成子作为 HydE 进一步加工的最终产物。

更新日期：2021-10-12

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